Abstract

Background: Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder with onset in childhood and is characterized by obsessions (recurrent, intrusive, persistent thoughts, impulses and/or ideas that often cause anxiety or distress) and compulsions (ritualized and stereotypic behaviours or mental acts that are often performed to relieve anxiety or distress associated with obsessions). Although OCD is a heritable disorder, its complex molecular etiology is poorly understood.

Methods: We combined enrichment analyses and an elaborate literature review of the top-ranked genes emerging from the 2 published genome-wide association studies of OCD and candidate genes implicated through other evidence in order to identify biological processes that, when dysregulated, increase the risk for OCD.

Limitations: This study is a first attempt to integrate molecuar information from different sources in order to identify biological mechanisms underlying OCD etiology. Our findings are constrained by the limited information from hypothesis-free studies and the incompleteness and existing limitations of the OCD literature and the gene function annotations of gene enrichment tools. As this study was solely based on in silico analyses, experimental validation of the provided hypotheses is warranted.

Conclusion: Our work suggests a key role for insulin and insulin-related signalling in OCD etiology and — if confirmed by independent studies — could eventually pave the way for the development of novel OCD treatments.

Acknowledgements: The authors thank the families who made all the genetic studies of OCD possible and the many investigators whose work drives the OCD genetics field forward. The authors also thank the anonymous reviewers for their useful comments and suggestions regarding text revision. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement n°278948 (TACTICS). This funding organization has had no involvement with the conception, design, data analysis and interpretation, review and/or any other aspects relating to this paper.

Contributors: I. van de Vondervoort, G. Poelmans, J. Glennon and B. Franke designed the study. I. van de Vondervoort and G. Poelmans acquired the data, which all authors analyzed. I. van de Vondervoort, G. Poelmans and B. Franke wrote the article, which all authors reviewed and approved for publication.